Chunyan Li

Intelligent wearable theranostic systems are advancing personalized health care by enabling continuous monitoring and proactive therapy. However, managing chronic oral diseases such as caries and periodontitis is challenging due to the oral cavity’s complex, spatially heterogeneous microenvironments and limited space for powered intraoral electronics. To address this, we developed a wireless, battery-free, and wearable intelligent therapeutic aligner (WiB-ITA) that integrates a butterfly-inspired dual-sided flexible integrated theranostic electrode array (iTEA) to simultaneously monitor compartment-matched pH and nitrite and electrochemically gate on-demand antimicrobial release. The system is powered and commanded via a relay-assisted near-field communication (NFC)–Bluetooth low energy (BLE) dual-hop link, enabling stable battery-free operation across tooth positions and full-arch usability. Validated from in vitro to preliminary human studies, WiB-ITA establishes a scalable, compartment-matched intraoral closed-loop theranostic framework. This integrated theranostic platform represents a breakthrough in personalized oral health care and provides a paradigm for managing other chronic conditions.

Periodontitis is a polymicrobial disease driven by metabolic interdependencies, wherein commensal bacteria fuel the virulence of keystone pathogens like Porphyromonas gingivalis ( P. gingivalis ). In particular, Veillonella parvula ( V. parvula ) supplies essential nutrients to the keystone pathogen P. gingivalis , enabling its virulence even at low abundance. Therefore, targeting V. parvula nitrate metabolism to deprive P. gingivalis of nutrients and attenuate its virulence represents a promising therapeutic strategy for controlling periodontitis progression. We engineered L‐cysteine‐capped ruthenium nanoclusters (Ru NCs) that efficiently reduce nitrate to ammonium under 660 nm light. This photocatalytic conversion depleted the bioavailable nitrate pool associated with V. parvula metabolism, disrupting amino acid production and quorum‐sensing‐related support for P. gingivalis . Consequently, Ru NCs potently reduced biofilm biomass and thickness, suppressed P. gingivalis activity, and downregulated its key virulence genes (RgpA/B , Kgp , FimA ). Multiomics analyses supported nitrate‐dependent metabolic collapse in V. parvula , which was associated with downstream energy and biosynthetic impairment in P. gingivalis . In a rat periodontitis model, light‐activated Ru NCs attenuated alveolar bone loss, preserved collagen, and shifted the local cytokine profile from pro‐inflammatory (IL‐6) to anti‐inflammatory (Arg‐1). This work provides a proof‐of‐concept strategy for targeting defined interspecies metabolic interactions, offering a new paradigm for microbiome‐targeted therapy.

We discuss recent advances in photo-responsive theranostic nanoplatforms for dental disease management and evaluate their mechanisms, performance and future design principles.

Fluorescent nanosensors based on ligand-engineered gold nanoclusters (Au NCs), guiding antibiotic therapy, offer a promising approach for rapid bacterial detection. Here, we developed dual-ligand-modified Au NCs with 6-azido-2-thiothymidine (ATT) and L-arginine (Arg), in which Arg modification enhanced the photoluminescence (PL) intensity compared to ATT-Au NCs. This enables a linear response (R² > 0.97) to bacterial concentrations (10⁵–10⁹ CFU mL⁻¹) within 30 minutes. Targeted metabolomics revealed that bacterial Arg deiminase metabolized Arg to citrulline, triggering PL quenching. Furthermore, it demonstrates the quantitative relationship between bacterial metabolic status and alterations in PL signals. The signal changes were visible under UV light and can also be quantified using a smartphone app (Light Meter). The detection limit reached 10⁵ CFU mL⁻¹. In vivo experiments confirmed that the probe can monitor wounds infected with Staphylococcus aureus (S. aureus), with minimal interference from biological matrices. This work highlights a portable, cost-effective strategy for point-of-care bacterial detection, addressing critical needs in clinical diagnostics.

Periodontitis involves hyperactivated stromal cells that recruit immune cells, exacerbating inflammation. This study presents an ATP-responsive metal–organic framework (Mg/Zn-MOF) designed for periodontitis treatment, utilizing ion interference to modulate immune responses and prevent tissue destruction. Addressing the challenges of synergistic ion effects and targeted delivery faced by traditional immunomodulatory nanomaterials, the Mg/Zn-MOF system is activated by extracellular ATP—a pivotal molecule in periodontitis pathology—ensuring targeted ion release. Magnesium and zinc ions released from the framework synergistically inhibit membrane pore formation by attenuating Gasdermin D (GSDMD) expression and activation. This action curtails pyroptosis, lactate dehydrogenase and IL-1β release, thwarting the onset of inflammatory cascades. Mechanistically, Mg/Zn-MOF intervenes in both the NLRP3/Caspase-1/GSDMD and Caspase-11/GSDMD pathways to mitigate pyroptosis. In vivo assessments confirm its effectiveness in diminishing inflammatory cell infiltration and preserving collagen integrity, thereby safeguarding against periodontal tissue damage and bone loss. This investigation highlights the promise of ion-interference strategies in periodontitis immunotherapy, representing a significant stride in developing targeted therapeutic approaches.

Metal nanoclusters (NCs) are well‐recognized novel nano‐agents that hold great promise for applications in nanomedicine because of their ultrafine size, low toxicity, and high renal clearance. As foreign substances, however, an in‐depth understanding of the bioresponses to metal NCs is necessary but is still far from being realized. Herein, this review is deployed to summarize the biofates of metal NCs at various biological levels, emphasizing their multiscale bioresponses at the molecular, cellular, and organismal levels. In the parts‐to‐whole schema, the interactions between biomolecules and metal NCs are discussed, presenting typical protein‐dictated nano–bio interfaces, hierarchical structures, and in vivo trajectories. Then, the accumulation, internalization, and metabolic evolution of metal NCs in the cellular environment and as‐imparted theranostic functionalization are demonstrated. The organismal metabolism and transportation processes of the metal NCs are subsequently distilled. Finally, this review ends with the conclusions and perspectives on the outstanding issues of metal NC‐mediated bioresponses in the near future. This review is expected to provide inspiration for tailoring the customization of metal NC‐based nano‐agents to meet practical requirements in different sectors of nanomedicine.

Background: Periodontal disease, an oral disease that initiates with plaque biofilm infection, affects 10% of the global population. Due to the complexity of tooth root anatomy, biofilm resistance and antibiotic resistance, traditional mechanical debridement and antibiotic removal of biofilms are not ideal. Nitric oxide (NO) gas therapy and its multifunctional therapy are effective methods to clear biofilms. However, large and controlled delivery of NO gas molecules is currently a great challenge.

Sulfate radicals (SO₄⁻·) play important biological roles in biomedical and environmental engineering, such as antimicrobial, antitumor, and disinfection. Compared with other common free radicals, it has the advantages of a longer half-life and higher oxidation potential, which could bring unexpected effects. These properties have prompted researchers to make great contributions to biology and environmental engineering by exploiting their properties. Peroxymonosulfate (PMS) and peroxydisulfate (PDS) are the main raw materials for SO₄⁻· formation. Due to the remarkable progress in nanotechnology, a large number of nanomaterials have been explored that can efficiently activate PMS/PDS, which have been used to generate SO₄⁻· for biological applications. Based on the superior properties and application potential of SO₄⁻·, it is of great significance to review its chemical mechanism, biological effect, and application field. Therefore, in this review, we summarize the latest design of nanomaterials that can effectually activate PMS/PDS to create SO₄⁻·, including metal-based nanomaterials, metal-free nanomaterials, and nanocomposites. Furthermore, we discuss the underlying mechanism of the activation of PMS/PDS using these nanomaterials and the application of SO₄⁻· in the fields of environmental remediation and biomedicine, liberating the application potential of SO₄⁻·. Finally, this review provides the existing problems and prospects of nanomaterials being used to generate SO₄⁻· in the future, providing new ideas and possibilities for the development of biomedicine and environmental remediation.